Comparative analysis of cytolethal distending toxin (cdt) genes among Campylobacter jejuni, C. coli and C. fetus strains.

The cytolethal distending toxin (cdt) gene clusters of Campylobacter coli strain Co1-243 and C. fetus strain Col-187 were cloned and sequenced to understand the importance of Cdt as a virulence factor. The cdt genes of C. coli and C. fetus consist of three closely linked genes termed cdtA, cdtB, cdtC whose sizes are 774, 801, and 570 bp, and 702, 798, and 546 bp, respectively. The homologies of each subunit of cdt genes between C. jejuni and C. coli, C. jejuni and C. fetus, or C. coli and C. fetus are 59.6%, 40.3%, or 46.5% for cdtA, 70.2%, 62.4%, or 61.3% for cdtB, 61.3%, 52.3%, or 50.1% for cdtC, respectively. Colony hybridization assay revealed that the genes homologous to the cdtABC gene were distributed in all 27, 19, 20 strains of C. jejuni, C. coli, and C. fetus, respectively, isolated from patients and animals in species-specific manner. Furthermore, nucleotide sequence of the cdt operon, including flanking region, of 10 strains of each species indicated that though the size of the cdtB gene was conserved in each species, those of cdtA and cdtC genes varied particularly among C. coli strains. Amino acid residues demonstrated to be important for toxin activity in CdtB, corresponding to H152, D185, D222, D258, H259 in Cj-CdtB, were also conserved in Cc-CdtB and Cf-CdtB. The cdt gene cluster was located in different sites among different species but in the same site of genomes of the same species. Cdt activity produced by C. jejuni and C. fetus varied among strains, however, any C. coli strains exhibited Cdt activity on HeLa cells. These data indicate that the cdt gene may have a potential for virulence factor at least in C. jejuni and C. fetus.